Prenatal methylazoxymethanol treatment in rats produces brain abnormalities with morphological similarities to human developmental brain dysgeneses

Claudia Colacitti, Giulio Sancini, Silvia DeBiasi, Silvana Franceschetti, Antonio Caputi, Carolina Frassoni, Flaminio Cattabeni, Giuliano Avanzini, Roberto Spreafico, Monica Di Luca, Giorgio Battaglia

Research output: Contribution to journalArticlepeer-review

Abstract

A double methylazoxymethanol (MAM) intraperitoneal injection was prenatally administered to pregnant rats at gestational day 15 to induce developmental brain dysgeneses. Thirty adult rats from 8 different progenies were investigated with a combined electrophysiological and neuroanatomical analysis. The offspring of treated dams was characterized by extensive cortical layering abnormalities, subpial bands of heterotopic neurons in layer I, and subcortical nodules of heterotopic neurons extending from the periventricular region to the hippocampus and neocortex. The phenotype of cell subpopulations within the heterotopic structures was analyzed by means of antibodies raised against glial and neuronal markers, calcium binding proteins, GABA, and AMPA glutamate receptors. Neurons within the subcortical heterotopic nodules were characterized by abnormal firing properties, with sustained repetitive bursts of action potentials. The subcortical nodules were surrounded by cell clusters with ultrastructural features of young migrating neurons. The immunocytochemical data suggested, moreover, that the subcortical heterotopia were formed by neurons originally committed to the neocortex and characterized by morphological features similar to those found in human periventricular nodular heterotopia. The present study demonstrates that double MAM treatment at gestational day 15 induces in rats developmental brain abnormalities whose anatomical and physiological features bear resemblance to those observed in human brain dysgeneses associated with intractable epilepsy. Therefore, MAM treated rats could be considered as useful tools in investigating the pathogenic mechanisms involved in human developmental brain dysgeneses.

Original languageEnglish
Pages (from-to)92-106
Number of pages15
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number1
Publication statusPublished - Jan 1999

Keywords

  • Band heterotopia
  • Cerebral migrational and organizational disorders
  • Cortical dysplasia
  • Neuronal differentiation
  • Neuronal migration
  • Periventricular heterotopia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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